You are on page 1of 2

Revision Bulletin

Official March 1, 2010 Diclofenac 1

Medium, Apparatus, and ProcedureProceed as directed for


Diclofenac Sodium Extended-Release Test 1.
Tablets Times: 1, 2, 4, 6, and 10 hours.
TolerancesThe percentages of the labeled amount of
C14H10Cl2NNaO2 dissolved at the times specified conform to Accep-
Diclofenac Sodium Extended-Release Tablets contain tance Table 2.
not less than 90.0 percent and not more than 110.0 per-
cent of the labeled amount of diclofenac sodium Time (hours) Amount dissolved
(C14H10Cl2NNaO2). 1 not more than 28%
2 between 20% and 40%
Packaging and storagePreserve in well-closed containers. Store 4 between 35% and 60%
at controlled room temperature, and protect from light. 6 between 50% and 80%
LabelingWhen more than one Dissolution Test is given, the la- 10 not less than 65%
beling states the Dissolution Test used only if Test 1 is not used.
USP Reference standards 11USP Diclofenac Sodium RS. USP
TEST 3If the product complies with this test, the labeling indi-
Diclofenac Related Compound A RS.
cates that it meets USP Dissolution Test 3.
Identification
Medium and ProcedureProceed as directed for Test 1.
A: The retention time of the major peak in the chromatogram
of the Assay preparation corresponds to that in the chromatogram Apparatus 1: 100 rpm.
of the Standard preparation, as obtained in the Assay. Times: 2, 4, 8, and 16 hours.
B: Thin-Layer Chromatographic Identification Test 201 TolerancesThe percentages of the labeled amount of
Solvent system: methanol, toluene, glacial acetic acid C14H10Cl2NNaO2 dissolved at the times specified conform to Accep-
(40 : 60 : 0.5). tance Table 2.
Test solutionFinely powder not fewer than 10 Tablets. Accu-
rately weigh a portion of the powder, equivalent to about 50 mg of Time (hours) Amount dissolved
diclofenac sodium, and transfer to a 25-mL volumetric flask. Add 2 between 22% and 42%
about 15 mL of methanol, sonicate for 10 minutes, shake by me- 4 between 34% and 61%
chanical means for 10 minutes, dilute with methanol to volume, and 8 between 52% and 82%
mix. Centrifuge this solution, and use the clear supernatant as the
Test solution. 16 not less than 73%
Standard solutionAccurately weigh about 50 mg of USP
Diclofenac Sodium RS into a 25-mL volumetric flask. Add 10 mL TEST 4If the product complies with this test, the labeling indi-
of methanol, shake by mechanical means for 10 minutes, dilute with cates that it meets USP Dissolution Test 4.
methanol to volume, and mix. Medium and Procedure Proceed as directed for Test 1.
Apparatus 1: 100 rpm.
Change to read:
Times: 2, 4, 8, and 16 hours.
Dissolution 711 TolerancesThe percentages of the labeled amount of
TEST 1 C14H10Cl2NNaO2 dissolved at the times specified conform to Accep-
tance Table 2.
Medium: 0.05 M phosphate buffer, pH 7.5; 900 mL.
Apparatus 2: 50 rpm; use wire sinkers.
Time (hours) Amount dissolved
Times: 1, 5, 10, 16, and 24 hours.
2 between 20% and 40%
ProcedureDetermine the amount of C14H10Cl2NNaO2 dissolved
by employing UV absorption at the wavelength of maximum ab- 4 between 35% and 55%
sorbance at about 276 nm on filtered portions of the solution under 8 between 60% and 85%
test, suitably diluted with Medium, if necessary, in comparison with 16 not less than 85% (RB 1-Mar-2010)
a Standard solution having a known concentration of USP
Diclofenac Sodium RS in the same Medium. (RB 1-Mar-2009)
TolerancesThe percentages of the labeled amount of Uniformity of dosage units 905: meet the requirements.
C14H10Cl2NNaO2 dissolved at the times specified conform to Accep- Assay[NOTEProtect the Assay preparation, Standard prepara-
tance Table 2. tion, and System suitability solution from light.]
Diluent: a mixture of acetonitrile and water (43 : 57).
Time (hours) Amount dissolved 0.05 M Monobasic potassium phosphate bufferDissolve 6.8 g
of monobasic potassium phosphate in 950 mL of water, adjust with
1 between 15% and 35% dilute phosphoric acid or dilute potassium hydroxide solution to a
5 between 45% and 65% pH of 4.0 0.05, dilute with water to 1 L, and mix.
10 between 65% and 85% Mobile phasePrepare a filtered and degassed mixture of
16 between 75% and 95% acetonitrile, 0.05 M Monobasic potassium phosphate buffer, and
24 not less than 80% tetrahydrofuran (43 : 57 : 2). Make adjustments if necessary (see
System Suitability under Chromatography 621).
Diclofenac related compound A solutionDissolve an accurately
TEST 2If the product complies with this test, the labeling indi- weighed quantity of USP Diclofenac Related Compound A RS in
cates that it meets USP Dissolution Test 2. Diluent, and quantitatively dilute with Diluent to obtain a solution
having a known concentration of about 200 g per mL.

2009 The United States Pharmacopeial Convention All Rights Reserved.


Revision Bulletin
2 Diclofenac Official March 1, 2010

Standard preparationDissolve an accurately weighed quantity directed for Procedure: the relative retention times are about 0.9 for
of USP Diclofenac Sodium RS in Diluent, and quantitatively dilute diclofenac related compound A and 1.0 for diclofenac; and the reso-
with Diluent to obtain a solution having a known concentration of lution, R, between the diclofenac peak and the diclofenac related
about 200 g per mL. compound A peak is not less than 2.0. Inject 20 L of the Standard
System suitability solutionTransfer 10 mL of the Standard preparation into the chromatograph, and record the peak responses
preparation and 5 mL of Diclofenac related compound A solution as directed for Procedure: the tailing factor of the diclofenac peak
to a 20-mL volumetric flask. Dilute with Diluent to volume, and is not more than 2.0; and the relative standard deviation of the
mix. diclofenac peak for replicate injections is not more than 2.0%.
Assay preparationPowder not fewer than 20 Tablets, and trans- ProcedureSeparately inject equal volumes (about 20 L) of the
fer an accurately weighed portion of the powder, equivalent to Standard preparation and the Assay preparation into the chromato-
about 100 mg of diclofenac sodium, to a 100-mL volumetric flask, graph, record the chromatograms, and measure the area responses
add about 50 mL of Diluent, sonicate for about 15 minutes, then for the major peaks. Calculate the quantity, in mg, of diclofenac
shake by mechanical means for 15 minutes. Add a few drops of sodium (C14H10Cl2NNaO2) in the portion of Tablets taken by the
methanol to remove the foam, dilute with Diluent to volume, and formula:
mix. Transfer 10.0 mL of the supernatant to a 50-mL volumetric
flask, dilute with Diluent to volume, and mix. 500C(rU / rS)
Chromatographic system (see Chromatography 621)The liq- in which C is the concentration, in mg per mL, of USP Diclofenac
uid chromatograph is equipped with a 254-nm detector and a 4.6- Sodium RS in the Standard preparation; and rU and rS are the
mm 15-cm column that contains 5-m packing L1. The flow rate diclofenac peak responses obtained from the Assay preparation and
is about 1.5 mL per minute. Inject 40 L of the System suitability the Standard preparation, respectively.
solution into the chromatograph, and record the peak responses as

2009 The United States Pharmacopeial Convention All Rights Reserved.